WAVE2 is regulated by multiple phosphorylation events within its VCA domain.
Cell Motility and the Cytoskeleton
The (Wiskott-Aldrich Syndrome Protein)-family verprolin homologous protein (WAVE) family of proteins occupies a pivotal position in the cell, converting extracellular signals into the formation of branched filamentous (F) actin structures. WAVE proteins contain a verprolin central acidic (VCA) domain at their C-terminus, responsible for binding to and activating the Arp2/3 complex, which in-turn nucleates the formation of new actin filaments. Here we identify five Casein Kinase 2 (CK2) phosphorylation sites within the VCA domain of WAVE2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the Arp2/3 complex. Phosphorylation of ser 482 and 484 specifically inhibits the activation of the Arp2/3 complex by the WAVE2 VCA domain, but has no effect on the affinity for the Arp2/3 complex when the other phosphorylation sites are occupied. We demonstrate phosphorylation of all five sites on endogenous WAVE2 and show that their mutation to non-phosphorylatable alanine residues inhibits WAVE2 function in vivo, inhibiting cell ruffling and disrupting the integrity of the leading edge of migrating cells.
addresses: Department of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol, United Kingdom.
notes: PMCID: PMC2798068
OnlineOpen Article. This is a copy of an article published in Cell Motility and the Cytoskeleton. This journal is available online at: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1949-3592
The definitive version is available at www3.interscience.wiley.com
Cell Motility and the Cytoskeleton, 2009, Vol. 66, Issue 1, pp. 36 - 47
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